The present invention relates to medical diagnostic techniques, and particularly to methods for identifying certain neurological and psychiatric disorders.
The presence of a great variety of neuron-specific phosphoproteins in nervous tissue supports the view that protein phosphorylation plays many roles in neuronal function. Protein phosphorylation is an important mechanism in neuronal signal transduction. Triggering mechanisms for activation of protein phosphorylation include many established second messengers (cAMP, cGMP, calcium) which are generated by interaction of neurotransmitters with their receptors. The second messengers, in turn, activate protein kinases (protein-phosphorylating enzymes) which transfer phosphate from adenosine triphosphate (ATP) to substrate proteins. These substrate proteins go on to mediate many of the physiological effects attributed to the transmitter-receptor interaction.
The protein composition of cerebrospinal fluid is largely derived from serum proteins which leak into the subarachnoid space through imperfections in the blood brain barrier,such as the area postrema, and perhaps across the choroid plexus, the richly vascular structure through which cerebrospinal fluid is generated as an ultrafiltrate. Some proteins, such as immunoglobulins, may be generated in the subarachnoid space during inflammation. Since the cerebrospinal fluid bathes the surfaces of cerebral and cerebeller cortices, the caudate, brainstem and spinal cord, some contribution of these structures to total cerebrospinal fluid protein might be expected. Indeed, peptide neurotransmitters have been identified in cerebrospinal fluid and are presumably neuron-derived though a serum source has not been excluded. Otherwise, however, cerebrospinal protein chemistry has been notoriously unyielding of neuron-specific information.
Although abnormal proteins have been identified in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease, See Harrington etal., New. Eng. J. Med., 315, pp 279-283 (1986), no correlative method presently exists which will identify a neurological or psychiatric disorder based upon the proteins present in a patient's cerebrospinal fluid.